Liver resection for multimodal treatment of breast cancer metastases: identification of prognostic factors.

BACKGROUND: Liver resection (LR) within a multimodal treatment concept of hepatic metastases (HM) that results from breast cancer has been controversially discussed. The aim of this study was to evaluate the outcome of LR in patients with hepatic breast cancer metastases. METHODS: Prospectively collected data from 41 consecutive patients who underwent LR for HM between 1999 and 2008 were analyzed retrospectively. Univariate and multivariate analyses were performed to assess potential prognostic factors. RESULTS: Segmental resection was performed in 46% and major hepatectomy in 54% of patients. The postoperative mortality rate was 0%. At a median follow-up of 34 months, 26 patients were alive. The median and 5-year overall survival rates after LR were 58 months and 48%, respectively. The median and 5-year disease-free survivals were 34 months and 31%, respectively. The intrahepatic recurrence-free 5-year survival was 62%. The median survival from time of diagnosis of HM was 79 months. The positive resection margin as well as a disease-free interval between the treatment of the primary tumor and the diagnosis of HM < 1 year were independent predictors of overall survival. CONCLUSIONS: LR of hepatic breast cancer metastases within a multimodal treatment concept is a safe procedure in well-selected patients. Both a short time interval to the development of HM and positive resection margins after LR are strongly associated with worse long-term survival.

Quality of life ten and more years after restorative proctocolectomy for patients with familial adenomatous polyposis coli.

PURPOSE: Few studies on long-term quality of life after restorative proctocolectomy and ileal pouch-anal anastomosis have been published. Most of them survey a mixed patient population of familial adenomatous polyposis and ulcerative colitis. The present study analyzes long-term results more than 10 years after ileal pouch-anal anastomosis for patients with familial adenomatous polyposis, exclusively. METHODS: One hundred thirty-five patients who underwent ileal pouch-anal anastomosis more than 10 years ago were identified from the prospective familial adenomatous polyposis registry at Heidelberg University hospital. They received the German version of the health-specific Short Form 36 Health Survey and the disease-specific Gastrointestinal Quality of Life Index by mail. To assess the impact of disease-specific factors, 10 questions asking for ability to work, current medication, pouchitis, and extracolonic manifestations of familial adenomatous polyposis were added to the Gastrointestinal Quality of Life Index questionnaire. RESULTS: Among 84 patients who answered the questionnaires the median follow-up was 13.4 years (range, 10.3-23.8 y).The results of the Short Form 36 Health Survey were comparable to a German normative population in all dimensions, whereas the overall score for the Gastrointestinal Quality of Life Index was significantly reduced compared with healthy individuals (111.8 vs 120.8, P = .0014). Carcinoma at the time of ileal pouch-anal anastomosis, desmoid tumors, or duodenal adenomas had no significant influence on quality of life. More than 7 bowel movements during the daytime were found to reduce quality of life significantly (103.5 vs 115, P = .0127). More than 2 defecations per night diminished the score further (101 vs 125, P < .0001). Patients younger than 40 years at the time of ileal pouch-anal anastomosis had significantly better results than older patients (120 vs 109.5, P = .0076). CONCLUSION: Ileal pouch-anal anastomosis is a safe surgical procedure with a high quality of life comparable to that of a normative population after long-term follow-up of patients with familial adenomatous polyposis.

Long-term outcome 10 years or more after restorative proctocolectomy and ileal pouch-anal anastomosis in patients with ulcerative colitis.

PURPOSE: The aim of this study was to assess quality of life (QOL) in a long-term follow-up of patients with ulcerative colitis (UC) 10 years and more after ileal pouch-anal anastomosis (IPAA) to correlate these results with pouch function and to assess the long-term pouch failure rate. METHODS: In a unicentric study, 294 consecutive patients after IPAA between 1988 and 1996 were identified from a prospective database. QOL was evaluated according to the validated Gastrointestinal Quality of Life Index (GIQLI). RESULTS: Overall median follow-up was 11.5 years. Thirty-seven patients experienced pouch failure (12.6%). The rates of ileal pouch success after 5, 10 and 15 years were 92.3%, 88.7% and 84.5%. According to the GIQLI, patients with a functioning pouch achieved a mean score of 107.8, reflecting a decrease of QOL of 10.8% compared to a healthy population. There were significant negative correlations between QOL and an age of >50 years (p < 0.05), pouchitis, perianal inflammation and increased stool frequency (p < 0.0001). CONCLUSIONS: QOL and functional results of patients with UC 10 years or more after IPAA were acceptable; however, those were reduced when compared to a healthy population. Pouch failure rate still increases up to 15.5% 15 years after IPAA. This result represents an important issue in providing patients with comprehensive preoperative information.

Hepatic platelet and leukocyte adherence during endotoxemia.

INTRODUCTION: Liver microcirculation disturbances are a cause of hepatic failure in sepsis. Increased leukocyte-endothelial interaction, platelet adherence and impaired microperfusion cause hepatocellular damage. The time course and reciprocal influences of ongoing microcirculatory events during endotoxemia have not been clarified. METHODS: Male Wistar rats (232 +/- 17 g) underwent cecal ligation and puncture (CLP). Intravital microscopy (IVM) was performed 0, 1, 3, 5, 10 and 20 hours after CLP. Mean erythrocyte velocity, leukocyte and platelet rolling in postsinusoidal venules and sticking of leukocytes and platelets in postsinusoidal venules and hepatic sinusoids were determined. Heart rate (HR), mean arterial pressure (MAP) and portal venous blood flow (PBF) were measured. Blood count and investigation of hepatic enzyme release was performed after each IVM time point. RESULTS: Hepatic platelet-endothelial adherence in liver sinusoids and postsinusoidal venules occurred one hour after the induction of endotoxemia. Leukocyte-endothelial interaction started three to five hours after CLP. A decrease of hepatic microperfusion could be observed at three hours in sinusoids and ten hours in postsinusoidal venules after CLP, although PBF was reduced one hour after CLP. HR remained stable and MAP decreased ten hours after CLP. Hepatic enzymes in blood were significantly elevated ten hours after CLP. CONCLUSION: Hepatic platelet-endothelial interaction is an early event during endotoxemia. Leukocyte adherence occurs later, which underlines the probable involvement of platelets in leukocyte recruitment. Although PBF is reduced immediately after CLP, the later onset of hepatic microperfusion decrease makes the existence of autoregulatory liver mechanisms likely.

The vital threat of an upper gastrointestinal bleeding: Risk factor analysis of 121 consecutive patients.

AIM: To analyze the importance in predicting patients risk of mortality due to upper gastrointestinal (UGI) bleeding under today's therapeutic regimen. METHODS: From 1998 to 2001, 121 patients with the diagnosis of UGI bleeding were treated in our hospital. Based on the patients' data, a retrospective multivariate data analysis with initially more than 270 single factors was performed. Subsequently, the following potential risk factors underwent a logistic regression analysis: age, gender, initial hemoglobin, coumarines, liver cirrhosis, prothrombin time (PT), gastric ulcer (small curvature), duodenal ulcer (bulbus back wall), Forrest classification, vascular stump, variceal bleeding, Mallory-Weiss syndrome, RBC substitution, recurrent bleeding, conservative and surgical therapy. RESULTS: Seventy male (58%) and 51 female (42%) patients with a median age of 70 (range: 21-96) years were treated. Their in-hospital mortality was 14%. While 12% (11/91) of the patients died after conservative therapy, 20% (6/30) died after undergoing surgical therapy. UGI bleeding occurred due to duodenal ulcer (n = 36; 30%), gastric ulcer (n = 35; 29%), esophageal varicosis (n = 12; 10%), Mallory-Weiss syndrome (n = 8; 7%), erosive lesions of the mucosa (n = 20; 17%), cancer (n = 5; 4%), coagulopathy (n = 4; 3%), lymphoma (n = 2; 2%), benign tumor (n = 2; 2%) and unknown reason (n = 1; 1%). A logistic regression analysis of all aforementioned factors revealed that liver cirrhosis and duodenal ulcer (bulbus back wall) were associated risk factors for a fatal course after UGI bleeding. Prior to endoscopy, only liver cirrhosis was an assessable risk factor. Thereafter, liver cirrhosis, the location of a bleeding ulcer (bulbus back wall) and patients' gender (male) were of prognostic importance for the clinical outcome (mortality) of patients with a bleeding ulcer. CONCLUSION: Most prognostic parameters used in clinical routine today are not reliable enough in predicting a patient's vital threat posed by an UGI bleeding. Liver cirrhosis, on the other hand, is significantly more frequently associated with an increased risk to die after bleeding of an ulcer located at the posterior duodenal wall.

Expression of TRAIL and TRAIL receptors in colon carcinoma: TRAIL-R1 is an independent prognostic parameter.

PURPOSE: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) selectively induces apoptosis in cancer cells and may be involved in protection from metastases. TRAIL receptor (TRAIL-R) 1 and TRAIL-R2, but not TRAIL-R3 and TRAIL-R4, mediate apoptosis. We examined the expression of TRAIL and its receptors in normal and neoplastic colon epithelium, and studied its correlation with prognosis in colon cancer. EXPERIMENTAL DESIGN: Immunohistochemistry was performed on normal colon mucosa (n = 10), colon adenomas (n = 20), and R0-resected Unio Internationale Contra Cancrum stage II/III colon carcinomas (n = 129). Disease-free survival was examined by Kaplan-Meier estimates and the log-rank test. Prognostic factors were determined by multivariate Cox-analysis. RESULTS: In normal colon mucosa, TRAIL and TRAIL-R2 were expressed mostly in the surface epithelium, whereas TRAIL-R1 and TRAIL-R4 were detected all along the crypt axis. In adenomas, this expression pattern was mostly retained, although some adenomas also neoexpressed TRAIL-R3. In carcinomas, the expression of TRAIL and TRAIL receptors was much more variable. TRAIL, TRAIL-R2, TRAIL-R3, and TRAIL-R4 expression did not correlate statistically with disease-free survival (multivariate analysis: P = 0.54, P = 0.67, P = 0.45, and P = 0.69, respectively), but TRAIL-R1 expression was significantly associated with disease-free survival in colon cancer (multivariate analysis: P = 0.003). CONCLUSIONS: TRAIL-R1 is an independent prognostic factor in R0-resected Unio Internationale Contra Cancrum stage II/III colon cancer.

Effects of hemodynamic instability on brain death-induced prepreservation liver damage.

BACKGROUND: Brain death (BD) is an important multifactorial variable contributing to donor-specific liver damage. Our study aimed at assessing the specific effects of hemodynamic instability on systemic and hepatic parameters of perfusion, bowel ischemia, and oxidative stress in a porcine model of BD. METHODS: BD was induced in 16 pigs (German Landrace, 18-28 kg) in two groups (hypotension-BD [HYPO-BD], n=8; normotension-BD [NORM-BD], n=8), which were compared with control animals/living donors (n=6) for a period of 2 hr. We analyzed systemic hemodynamic parameters, bowel ischemia (intramucosal pH in the stomach and colon, plasma endotoxin levels, and endotoxin-neutralizing capacity [ENC]), and oxidative stress (total glutathione levels in erythrocytes) and compared the findings with hepatic parameters of perfusion (hepatic arterial flow, portal venous flow, and microperfusion) and liver oxidative stress (reduced glutathione and oxidized glutathione levels in the liver). RESULTS: Independent of the hemodynamic stability, liver macrocirculation and microcirculation decreased (HYPO-BD, 79+/-6 to 69+/-10 mL/100 g/min; NORM-BD, 81+/-10 to 73+/-7 mL/100 g/min; P<0.05). Hepatocellular damage (aspartate aminotransferase: NORM-BD, 49+/-20 units/L; HYPO-BD, 170+/-140 units/L; P<0.01) and hepatic oxidative stress (reduced glutathione in the liver/oxidized glutathione in the liver: NORM-BD, 29.4+/-2.3 to 13.0+/-1.3; HYPO-BD, 29.4+/-2.3 to 9.05+/-0.81; P<0.001) increased in both BD groups. With dependence on systemic hemodynamic parameters, bowel ischemia increased (intramucosal pH in the colon, 7.22+/-0.01, P<0.01; ENC, 75+/-14 endotoxin-neutralizing units/mL, P<0.01; endotoxin levels, 7+/-2 to 43+/-10 pg/mL, P<0.01) in the HYPO-BD group but not in the NORM-BD group or the living donor group. Furthermore, systemic oxidative stress was increased in the HYPO-BD group only (total glutathione levels in erythrocytes, 2.65+/-0.25 to 0.15+/-0.25 mM; P<0.01). CONCLUSIONS: During BD, liver-specific parameters (portal venous flow, microperfusion, aspartate aminotransferase activity, ENC, and hepatic oxidative stress) were compromised, independent of the hemodynamic status. Therefore, the systemic hemodynamic status does not reflect the functional status of the liver during BD.

Sensitization of sarcoma cells to doxorubicin treatment by concomitant wild-type adeno-associated virus type 2 (AAV-2) infection.

Doxorubicin-based chemotherapy is used in the treatment of sarcomas. Toxic side effects and poor response rates underline the demand for an improvement in current chemotherapeutic protocols. Recently, it has been reported that parvoviruses confer various antineoplastic properties to infected cells, and that adeno-associated virus type 2 (AAV-2) infection sensitizes malignant epithelial cells to radiation- or chemotherapy-based genotoxic treatment. Thus, we analyzed whether AAV-2 infection leads to an improved efficacy of doxorubicin chemotherapy in malignant mesenchymal cells, using 13 human sarcoma cell lines. Therapeutic effects were analyzed by measuring cell viability and proliferation (WST-1, colony forming, and propidium iodide assays). Additionally, permissivity for AAV-2 infection was determined by Southern dot blot analysis. AAV-2 infection strongly increased the efficacy of doxorubicin treatment in rhabdomyo-, fibro-, osteo- and chondrosarcoma cells in a dose-dependent manner. This effect was not observed in liposarcoma and synovial sarcoma cells, although a susceptability to AAV-2 infection was documented. Our results indicate that the sensitization effects towards genotoxic treatment exerted by non-pathogenic AAV-2 infection are not restricted to epithelial malignancies but may also be exploited for the improvement of chemotherapy in patients suffering from rhabdomyo-, fibro-, osteo-, or chondrosarcomas.

Reduction in mortality with delayed surgical therapy of severe pancreatitis.

The indications for surgery in acute pancreatitis have changed significantly in the past two decades. Medical charts of patients with acute pancreatitis treated at our institution were analyzed to assess the effects of changes in surgical treatment on patient outcomes. A total of 136 patients with radiologically defined severe pancreatitis were primarily treated or referred to our institution between 1980 and 1997. Severity of the disease (Ranson score), indications for surgical intervention, timing of surgery, and mortality rates were compared during three study periods: 1980 to 1985 (period I), 1986 to 1990 (period II), and 1991 to 1997 (period III). In period I patients underwent exploratory laparotomy if their clinical status did not improve markedly within 72 hours of admission to the hospital, whereas during period II surgery was reserved for patients who had secondary organ failure together with pancreatic necrosis seen on CT scan. During period III the aim was to operate as late as possible in the presence of pancreatic necrosis or when infected necrosis was suspected. The policy of limiting the indications for surgery resulted in a decrease in surgically treated patients from 68% to 33% (P < 0.001). Likewise, surgical intervention was performed later. In period I, 73% of operations were performed within 72 hours of admission, compared to 32% in period III (P = 0.008). The mortality rate for patients who underwent early surgery (within 72 hours) was higher than for those who underwent late surgical exploration of the abdomen (P = 0.02). Overall, the mortality rate for patients with severe pancreatitis was reduced from 39% to 12% (P = 0.003). Mortality among patients treated nonoperatively did not change significantly. The present study supports the policy of delayed surgery in severe acute pancreatitis. Early surgical intervention often results in unnecessary procedures with an increase in the number of deaths. Whenever possible, prolonged observation allows selection of patients who are likely to benefit from delayed surgery or nonoperative treatment.

Evaluation of visualization techniques for image-guided navigation in liver surgery.

A substantial component of an image-guided surgery system (IGSS) is the kind of three-dimensional (3D) presentation to the surgeon because the visual depth perception of the complex anatomy is of significant relevance for orientation. Therefore, we examined in this contribution four different visualization techniques, which were evaluated by eight surgeons. The IGSS developed by our group supports the intraoperative orientation of the surgeon by depicting a visualization of the spatially tracked surgical instruments with respect to intrahepatic vessels that have to be conserved vitally, the tumor, and preoperatively calculated resection planes. In the prelimenary trial presented here we examined the human ability to percept an intraoperative virtual scene and to solve given navigation tasks. The focus of the experiments was to measure the ability of eight surgeons to orientate intrahepaticaly and to transfer the percepted spatial relation to movements in real space. An autostereoscopic visualization with a prism-based display yielded that the navigation can be performed faster and more accurately than with the other visualization techniques.

Differential expression of toll-like receptor 3 and 5 in ileal pouch mucosa of ulcerative colitis patients.

BACKGROUND AND AIMS: The pathogenesis of pouchitis, major complication after restorative proctocolectomy, and ileal J pouch-anal anastomosis (IPAA) in patients with ulcerative colitis (UC) is still unclear. Changes in intraluminal bacterial colonization and correlated changes of pouch mucosa are thought to play an important role. Toll-like receptors (TLRs) as part of the innate immune system are capable of recognizing bacterial antigens. Their activation can lead to secretion of proinflammatory mediators. In this study, TLR2, 3, 4, and 5 expression profiles in the pouch mucosa of patients with UC and IPAA were analyzed and correlated with pouchitis. MATERIALS AND METHODS: Clinical symptoms, endoscopy, and histology were assessed in 35 patients using the Heidelberg Pouchitis Activity Score to classify patients as either having pouchitis or not. TLR mRNA expression in normal ileal mucosa and pouch mucosa was investigated by performing semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR). The results of RT-PCR were associated with the pouchitis score. RESULTS: In the analysis of all patients, TLR3 expression was decreased significantly whereas TLR5 expression was increased significantly in pouch mucosa compared to normal ileal mucosa (p-values 0.0076 and 0.016, respectively). A more detailed analysis upon dividing the patients into patients with and without pouchitis showed decreased TLR3 expression in the pouch mucosa only of patients without pouchitis (p-value=0.0067). TLR5 expression was increased in the pouch mucosa only of patients with pouchitis (p-value=0.023). No differences in TLR2 and 4 expression were found in either group. CONCLUSION: Differential expression of TLR3 and 5 suggests bacterial involvement in the pathogenesis of pouchitis in patients with UC.

Increased detection rate and potential prognostic impact of disseminated tumor cells in patients undergoing endorectal ultrasound for rectal cancer.

BACKGROUND: Hematogenous tumor-cell dissemination during diagnostic and therapeutic procedures in patients with colorectal cancer has been demonstrated. OBJECTIVE: The aim of this study was to investigate the extent of disseminated tumor cells in blood samples of rectal cancer patients after endorectal ultrasound and to determine its prognostic relevance. MATERIALS AND METHODS: Peripheral venous blood samples from 45 patients with rectal cancer were taken before and after endorectal ultrasound. Blood samples were examined using a reverse transcriptase-polymerase chain reaction (RT-PCR) assay to amplify cytokeratin 20 transcripts. Overall survival of the patients was calculated by the Kaplan-Meier method. RESULTS: Disseminated tumor cells were detected in peripheral blood samples of 17 of 45 (38%) patients before and after endorectal ultrasound. Circulating tumor cells were found in 11 of 45 (24%) patients only after endorectal ultrasound (p=0.006). There was a clear trend toward a worse prognosis in patients with tumor cells in blood samples after endorectal ultrasound, but this difference was not statistically significant. CONCLUSION: This study demonstrates significantly increased hematogenous tumor-cell dissemination after endorectal ultrasound in rectal cancer patients. Patients with tumor cells in blood samples after endorectal ultrasound tend to have a worse prognosis. The potential prognostic impact of this finding is presently unclear and has to be further validated in larger clinical trials.

Early re-laparotomy for post-operative complications is a significant risk factor for recurrence after ileocaecal resection for Crohn's disease.

BACKGROUND: There is evidence suggesting that stenosing and fistulising Crohn's diseases reflect specific entities. The aim of this study was to compare these two clinical presentations with regards to anastomotic recurrence after ileocaecal resection and identify other relevant risk factors. MATERIALS AND METHODS: One hundred consecutive patients undergoing isolated ileocaecal resection for Crohn's disease were included in this follow-up study. A recurrence was either defined endoscopically, on the basis of radiological examinations or on the basis of a re-operation. In addition, patients had to complain of clinical symptoms. Recurrence-free intervals were calculated by the Kaplan-Meier method. Univariate and multivariate analysis including previously identified risk factors for recurrence were performed. RESULTS: Of the 100 patients extracted from the database, 8 patients were lost to follow-up or refused participation. There was no mortality in this patient group, the morbidity was 16.3%. The recurrence rates after 5 and 9 years were 28.7% and 56.4%, respectively. Univariate analysis revealed re-laparotomy within the same hospital stay and length of resected specimen as significant factors for anastomotic recurrence. Both these factors were confirmed on multivariate analysis. But when analysing the observation period in detail, specimen length was not any more a significant factor in the later time period (1996-2000) compared to the earlier time period (1991-1995). The clinical presentation (fistulising vs stenosing) showed no significant influence on the recurrence rates. CONCLUSIONS: Patients with stenosing and fistulising Crohn's disease of the ileocaecal region have no difference in recurrence rates after resection. Re-laparotomy in the same hospital stay was an independent predictor of recurrence.

Detection of disseminated tumor cells in liver biopsies of colorectal cancer patients is not associated with a worse prognosis.

BACKGROUND: Liver metastases occur frequently in colorectal cancer and are probably caused by disseminated tumor cells having been trapped in the liver. The prognostic significance of hematogenous tumor cell dissemination has already been demonstrated for blood and bone marrow of patients with colorectal cancer. The aim of this study was to investigate the frequency and prognostic significance of disseminated tumor cells in liver biopsies of colorectal cancer patients. METHODS: Liver biopsies from 100 patients with UICC stage I-III colorectal cancer were taken prospectively during resection of the primary tumor. Liver biopsies obtained from 16 patients with benign gastrointestinal diseases served as negative controls. Liver samples from seven patients with liver cirrhosis were additionally taken. Liver biopsies were examined using a reverse transcriptase (RT)-PCR assay to amplify cytokeratin (CK) 20 transcripts. The median follow-up of the patients was 55 months. RESULTS: Disseminated tumor cells were detected in liver samples of 10/100 (10%) patients with UICC stage I-III colorectal cancer. Liver specimens from all seven patients with liver cirrhosis were CK 20-positive, whereas 16 patients with other benign gastrointestinal diseases were all CK 20-negative. There was no correlation between tumor cell detection in liver biopsies and survival of the patients. The only significant prognostic factor on uni- and multivariate analysis was the UICC stage. CONCLUSIONS: This study demonstrates that detection of disseminated tumor cells in liver samples from patients with UICC stage I-III colorectal cancer has no prognostic influence. UICC classification was the strongest prognostic factor in this patient series.

Prognostic impact of hematogenous tumor cell dissemination in patients with stage II colorectal cancer.

Adjuvant chemotherapy is not routinely recommended in patients with colorectal cancer stage UICC II. Some of these patients, however, develop recurrent disease. Therefore, valid prognostic criteria are needed to identify high-risk patients who might benefit from adjuvant therapy. Disseminated tumor cells, detected in blood and bone marrow, may prove to be a valid marker, however, the prognostic relevance of these cells remains debated. In our study, we examined the prognostic significance of disseminated tumor cells in blood and bone marrow of patients with stage II colorectal cancer. Ninety patients with potentially curative (R0) resection of colorectal cancer stage II were prospectively enrolled into the study. Bone marrow and blood samples were examined for disseminated tumor cells by CK 20 RT-PCR. Patient, tumor and treatment factors were analyzed as prognostic factors. Multivariate analysis confirmed tumor cell detection in blood (hazard ratio 2.1, p = 0.03) and T-category (hazard ratio 2.2, p = 0.02) to be independent prognostic factors for relapse-free survival. Tumor cell detection in postoperative blood samples (hazard ratio 7.7, p < 0.001) and number of removed lymph nodes (hazard ratio 6.4, p < 0.001) were independent prognostic factors for disease-specific survival. Detection of circulating tumor cells in blood samples of patients with stage II colorectal cancer identifies patients with poor outcome. This finding should be confirmed by further studies and could then be used as a basis for conducting a randomized trial evaluating the effect of adjuvant chemotherapy in stage II patients.

Relationships between volume, efficiency, and quality in surgery--a delicate balance from managerial perspectives.

Volume, efficiency, and quality in hospital care are often mixed in debate. We analyze how these dimensions are interrelated in surgical hospital management, with particular focus on volume effects: under financial constraints, efficiency is the best form of cost control. External perception of quality is important to attract patients and gain volumes. There are numerous explicit and implicit notions of surgical quality. The relevance of implicit criteria (functionality, reliability, consistency, customaziability, convenience) can change in the time course of hospital competition. Outcome data theoretically are optimal measures of quality, but surgical quality is multifactorially influenced by case mix, surgical technique, indication, process designs, organizational structures, and volume. As quality of surgery is hard to grade, implicit criteria such as customizability currently often overrule functionality (outcome) as the dominant market driver. Activities and volumes are inputs to produce quality. Capability does not translate to ability in a linear function. Adequate process design is important to realize efficiency and quality. Volumes of activities, degree of standardization, specialization, and customer involvement are relevant estimates for process design in services. Flow-orientated management focuses primarily on resource utilization and efficiency, not on surgical quality. The relationship between volume and outcome in surgery is imperfectly understood. Factors involve learning effects both on process efficiency and quality, increased standardization and task specialization, process flow homogeneity, and potential for process integration. Volume is a structural component to develop efficiency and quality. The specific capabilities and process characteristics that contribute to surgical outcome improvement should be defined and exported. Adequate focus should allow even small institutions to benefit from volume-associated effects. All volumes-based learning within standardized processes will finally lead to a plateauing of quality. Only innovations will then further improve quality. Possessing volume can set the optimal ground for continuous process research, subsequent change, innovation, and optimization, while volume itself appears not to be a quality prerequisite.

Detection of hematogenous tumor cell dissemination predicts tumor relapse in patients undergoing surgical resection of colorectal liver metastases.

OBJECTIVE: To examine the prognostic significance of disseminated tumor cells in blood and bone marrow of patients undergoing surgical resection of colorectal liver metastases. SUMMARY BACKGROUND DATA: Despite curative hepatic resection of colorectal liver metastases, a high percentage of patients develop tumor recurrence. These recurrences probably originate from disseminated tumor cells released into the circulation before or during surgery. METHODS: Thirty-seven patients with potentially curative (R0) resection of colorectal liver metastases were prospectively enrolled into the study. Preoperative bone marrow samples and preoperative, intraoperative, and postoperative blood samples were examined for disseminated tumor cells by CK20 RT-PCR. RESULTS: Tumor cells were detected in preoperative blood samples in 11 of 37 (30%) patients, in intraoperative blood samples in 17 of 37 (46%) patients, and in postoperative blood samples in 8 of 37 (22%) patients. Four of 25 (16%) patients tested positive for disseminated tumor cells in bone marrow samples. Median follow-up time for all patients was 38 months (range, 10-63 months). Multivariate analysis confirmed tumor cell detection in intraoperative blood (P = 0.009) and in bone marrow samples (P = 0.013) to be independent prognostic factors of tumor relapse. CONCLUSIONS: This is the first study demonstrating that detection of hematogenous tumor cell dissemination during hepatic resection of colorectal cancer metastases predicts tumor relapse. Detection of disseminated tumor cells may help to individualize adjuvant therapy for patients with colorectal liver metastases and to develop surgical strategies to prevent intraoperative hematogenous tumor cell shedding.

Results of limb-sparing surgery with vascular replacement for soft tissue sarcoma in the lower extremity.

OBJECTIVE: To evaluate limb-salvage surgery with vascular resection for lower extremity soft tissue sarcomas (STS) in adult patients and to classify blood vessel involvement. METHODS: Subjects were consecutive patients (median age, 56 years) who underwent vascular replacement during surgery of STS in the lower limb between January 1988 and December 2003. Blood vessel involvement by STS was classified as follows: type I, artery and vein; type II, artery only; type III, vein only; and type IV, neither artery nor vein (excluded from the analysis). Patient data were prospectively gathered in a computerized database. RESULTS: Twenty-one (9.9%) of 213 patients underwent vascular resections for lower limb STS. Besides 17 type I tumors (81.0%), 3 (14.3%) type II and 1 (4.7%) type III STS were diagnosed. Arterial reconstruction was performed for all type I and II tumors. Venous replacement in type I and III tumors was performed in 66.7% of patients. Autologous vein (n = 8) and synthetic (Dacron and expanded polytetrafluoroethylene; n = 12) bypasses were used with comparable frequency for arterial repair, whereas expanded polytetrafluoroethylene prostheses were implanted in veins. Morbidity was 57.2% (hematoma, thrombosis, and infection), and mortality was 5% (embolism). At a median follow-up of 34 months, the primary and secondary patency rates of arterial (venous) reconstructions were 58.3% (54.9%) and 78.3% (54.9%). Limb salvage was achieved in 94.1% of all cases. The 5-year local control rate and survival rate were 80.4% and 52%, respectively. We observed a 5-year metastasis-free survival rate of 37.7% and found vessel infiltration and higher tumor grade (low-grade vs intermediate grade and high grade tumors) to be negative prognostic factors at univariate and multivariate analysis. CONCLUSIONS: Long-term bypass patency rates, the high percentage of limb salvage, and the oncologic outcome underline the efficacy of en bloc resection of STS involving major vessels in the lower limb. Disease-specific morbidity must be anticipated. The classification of vascular involvement (type I to IV) is useful for surgical management.